DNA methylation serves an important role in the regulation of gene expression, and aberrant methylation has been suggested to contribute to the development of multiple tumor types, including gliomas. The extent to which methylation regulates gene expression in gliomas, as well as in the normal glial cells from which they are proposed to arise, is poorly understood. The Costello laboratory has developed a novel technique to assess the methylation status of CpG islands on a genome-wide scale using array technology. These arrays will be applied to purified progenitor and mature glial cells to identify the role of CpG island methylation in regulating gene expression in normal glia. These arrays will also be applied to the subtypes of diffuse glioma and the array analysis of normal glial cells will serve to distinguish normal cell-type specific methylation from truly aberrant methylation. These experiments will identify genes that are differentially methylated in gliomas, advancing our understanding of the mechanisms of glioma development and helping to identify potential therapeutic targets. Furthermore, comparison of methylation patterns may: 1) identify subtype-specific markers to aid in classifying gliomas and 2) provide clues to the cells of origin of gliomas.